The Role and Structure of the Carboxyl-terminal Domain of the Human Voltage-gated Proton Channel Hv1
The Role and Structure of the Carboxyl-terminal Domain of the Human Voltage-gated Proton Channel Hv1
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DOI：
10.1074/jbc.m109.040360
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发表时间：
2010-04-16
影响因子：
4.8
通讯作者：
Sun, Fei
中科院分区：
文献类型：
--
作者：
Li, Shu Jie;Zhao, Qing;Sun, Fei
电压门控质子通道Hv 1具有电压传感器域，但缺乏孔域。虽然已知Hv 1的C-末端结构域负责通道的二聚体结构，但其作用和结构尚不清楚。我们报告，全长Hv 1主要定位于细胞内室膜，而不是质膜。截断的N或C末端单独或两者一起显示，N-末端缺失不改变本地化，但删除的C末端单独或与N末端一起导致在整个细胞中的表达。这些结果表明，C端是必不可少的Hv 1定位，而不是N端。在C-末端结构域的2.0埃结构中，两个单体通过平行的C-螺旋卷曲螺旋形成二聚体，其中一个氯离子与Arg的N eta原子结合（264）。已经观察到蛋白质的pH依赖性结构变化，但它仍然是二聚体，与pH值无关。
The voltage-gated proton channel Hv1 has a voltage sensor domain but lacks a pore domain. Although the C-terminal domain of Hv1 is known to be responsible for dimeric architecture of the channel, its role and structure are not known. We report that the full-length Hv1 is mainly localized in intracellular compartment membranes rather than the plasma membrane. Truncation of either the N or C terminus alone or both together revealed that the N-terminal deletion did not alter localization, but deletion of the C terminus either alone or together with the N terminus resulted in expression throughout the cell. These results indicate that the C terminus is essential for Hv1 localization but not the N terminus. In the 2.0 angstrom structure of the C-terminal domain, the two monomers form a dimer via a parallel C-helical coiled-coil, in which one chloride ion binds with the N eta atom of Arg(264). A pH-dependent structural change of the protein has been observed, but it remains a dimer irrespective of pH value.